This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project investigates the consequences of the supramolecular structure of acetylcholinesterase (AChE) in the neuromuscular junction and other nicotinic cholinergic synapses. AChE must work extremely rapidly to clear the neurotransmitter acetylcholine (ACh) from such synapses after intercellular signaling has occurred. The AChE is organized into tetramers in the synaptic cleft, and in principle this could lead to inefficiencies if the monomers of enzyme compete strongly for ACh, since each monomer could effectively be "starved" for substrate.